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Aspirin Inhibition of Group VI Phospholipase A2 Induces Synthetic Lethality in AAM Pathway Down-Regulated

Kshama Pansare1, Bhabani Mohanty2, Ranjeeta Dhotre1

  • 1ICGC Lab, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India.

Cells
|January 11, 2022
PubMed
Abstract

Insights

Aspirin inhibits PLA2G6, impacting the arachidonic acid metabolism pathway in gingivobuccal squamous cell carcinoma. This reveals a new anti-tumor mechanism and potential for precision chemoprevention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Investigating the role of iPLA2/PLA2G6 in gingivobuccal squamous cell carcinoma (GB-SCC).
  • Exploring aspirin's potential for synthetic lethality-based chemoprevention in GB-SCC with a down-regulated arachidonic acid metabolism (AAM) pathway.

Purpose of the Study:

  • To elucidate the role of iPLA2/PLA2G6 in GB-SCC.
  • To ascertain aspirin's chemoprevention role in AAM pathway-down-regulated GB-SCC.

Main Methods:

  • In vitro assessment of aspirin's efficacy on GB-SCC cells (proliferation, apoptosis, migration, etc.) and RNA-seq.
  • Confirmation of PLA2G6 and AAM pathway inhibition via qPCR, Western blot, and immunofluorescence.
  • In vivo evaluation using NOD-SCID mice xenografts and immunohistochemistry.

Main Results:

  • Aspirin inhibits PLA2G6, affecting COX and LOX components of the AAM pathway.
  • Findings validated using PLA2G6 siRNA and immunohistochemical markers.
  • Pronounced effect in specific cell lines and xenografts suggests aspirin-induced synthetic lethality in AAM pathway-down-regulated GB-SCC.

Conclusions:

  • Aspirin exhibits anti-tumor effects via a novel PLA2G6 inhibition mechanism.
  • Aspirin's efficacy is dependent on the baseline AAM pathway status.
  • Results may guide precision prevention clinical trials for AAM pathway inhibitors.
Keywords:
PLA2G6arachidonic acid metabolism pathwayaspiringingivobuccal squamous cell carcinomaphospholipase

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